Monday, April 14, 2008

Atomic radiation protective drug

A news report caught my eye the other day -- that a developmental drug company, essentially funded by grants from the military, had successfully tested a drug (Protectan CBLB502) that could prevent or delay human death in the event of exposure to radiation from “a military attack with a nuclear device or terrorist action.” [Science 11 April 2008: Vol. 320. no. 5873, pp. 226 – 230] The military does not currently have any radiation-exposure medications.

The drug is an antidote to Acute Radiation Syndrome where blood cells, particularly immune cells called neutrophils, are killed off in such large numbers as to render the radiation-exposed subject totally vulnerable to infection. Also blood platelets, which facilitate blood clotting, are massively destroyed upon exposure to high-dose radiation. About 75% of monkeys exposed to a lethal dose of radiation survived when given Protectan CBLB502 compared to just 25% of untreated monkeys. The drug could also be used to treat cancer patients prior to or after radiation treatment as the drug didn’t interfere with treatment.

Another part of the news story caught my eye. It said “The proprietary Protectan family of compounds, which are derived from naturally occurring factors of microbes found in our bodies." Just how do you make a natural protein into a proprietary drug? Well, the drug is a genetically engineered version of flagellin. Flagellin is a protein found at the ends of some bacteria that invade the human body.

The Protectan CBLB502 molecule is a re-arranged flagellin protein. It is less toxic, or excites less of an immune response, than flagellin itself. When the body is exposed to flagellin the innate immune system is triggered. Flagellin itself will produce tolerance, that is, a less reactive immune response, which minimizes tissue damage. [American Journal Physiology Gastrointestinal Liver Physiology 2007: 292; G767-78]

Flagellin instilled into the nasal passages was found to almost completely prevent death among mice exposed to Yersinia pestis, the pathogen that causes The Plague. [Infection Immunity 2006: 74; 1113-20; Mechanisms Ageing Development 2008: 129; 271-81] In another experiment, mice given flagellin were completely protected from a lethal dose of tetanus toxin. [Infection Immunity 2006: 74; 694-702] Flagellin has been shown to activate the production of an antimicrobial peptide (protein) which is part of the innate immune system. [FASEB Journal Feb 8, 2008] This means activation of the human immune system is far more powerful than any known drug. Drugs or other natural molecules that activate the innate immune system would be supreme in the prevention or treatment of cancer and all infectious disease.

The maker of Protectan CBLB502 said it plans to begin studies in humans during the first half of 2008. We assume the drug company means it will test Protectan CBLB502 on humans undergoing radiation treatment for cancer. But how would patients ethically be exposed to lethal doses of radiation to completely test this drug for battlefield use?

Meanwhile, one cannot ignore a natural protectant produced in the human body to a different form of radiation --- vitamin D3 in response to exposure to solar ultraviolet radiation. Like flagellin, vitamin D3 produces an antibiotic peptide which protects against infection. Vitamin D produces cathelicidin, flagellin produces antimicrobial peptide S100A7c (psoriasin). [FASEB Journal Feb 8, 2008

Furthermore, vitamin D3 stimulates neutrophils. [Acta Paediatrica Scandinavia 1976 Nov; 65(6):695-9; Calcified Tissue International 1981; 33(6):673-6] Ironically, flagellin appears to induce a downregulation of NF-kappaB and p38 MAPK inflammatory enzymes that are necessary to convert vitamin D3 to 1,25 (OH)2D3 which controls the innate immune system. This may explain why certain germs evade the human immune system by inhibiting conversion of vitamin D3 to active forms that combat infection. [Journal Bone Mineral Research 21: 37-47, 2006] It appears the Protectan CBLB502 drug might make a person completely dependent upon the drug for proper function of the innate immune system.

The eye-catching part of the news story about Protectan CBLB502 is that the military now sees a radiation-protective drug as a priority and it is plausible it might be utilized in a wartime scenario, should it arise, prior to approval of this drug. Such a threatening scenario has been offered by responsible analysts who think it is possible the U.S. may be forced to use nuclear weapons in the Middle East to spare its army from being annihilated by overwhelming forces. (You can read these worrisome scenarios at: http://www.lewrockwell.com/lind/lind137.html and http://www.lewrockwell.com/roberts/roberts244.html )

Labels: flagellin, radiation, Vitamin D

posted by Knowledge of Health at 10:19 AM